Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, USA.
Atherosclerosis. 2010 Jan;208(1):50-5. doi: 10.1016/j.atherosclerosis.2009.06.013. Epub 2009 Jun 18.
Human aortic endothelial cells (HAEC) exposed to 50 microg/ml oxidized L-A-phosphatidylcholine B-arachidonoyl-gamma-palmitoyl (ox-PAPC) for 6h increased in interleukin-8 mRNA and protein levels. Preincubation of HAEC with the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitor, (20 microM), significantly inhibited ox-PAPC-stimulated interleukin-8 mRNA and protein levels. Mevalonate (200 microM) reversed the inhibition of ox-PAPC-stimulated mRNA and protein levels by lovastatin, indicating the inhibitory effect of lovastatin was due to inhibition of mevalonate synthesis. Addition of the geranylgeraniol (GGOL, 10 microM) but not farnesol (FOL, 10 microM), reversed the inhibitory effect of lovastatin on interleukin-8 mRNA and protein levels stimulated by ox-PAPC, indicating that lovastatin exerted its effect by inhibiting stores of geranylgeranyl pyrophosphate (GGPP) which are necessary for geranylgeranylation of proteins. These results suggest a new mechanism for lovastatin in preventing atherosclerosis by inhibiting the inflammatory response that takes place in the vascular wall.
人主动脉内皮细胞（HAEC）暴露于 50μg/ml 氧化 L-A-磷酸甘油胆碱 B-花生四烯酸-γ-棕榈酰（ox-PAPC）6 小时后，白细胞介素-8mRNA 和蛋白水平增加。HAEC 先用 3-羟基-3-甲基戊二酰基辅酶 A（HMG CoA）抑制剂（20μM）预处理，可显著抑制 ox-PAPC 刺激的白细胞介素-8mRNA 和蛋白水平。甲羟戊酸（200μM）逆转了洛伐他汀对 ox-PAPC 刺激的 mRNA 和蛋白水平的抑制作用，表明洛伐他汀的抑制作用是由于抑制了甲羟戊酸的合成。添加香叶基香叶醇（GGOL，10μM）但不是法呢醇（FOL，10μM），可逆转洛伐他汀对 ox-PAPC 刺激的白细胞介素-8mRNA 和蛋白水平的抑制作用，表明洛伐他汀通过抑制香叶基焦磷酸（GGPP）的储存来发挥作用，GGPP 是蛋白质异戊二烯化所必需的。这些结果表明，洛伐他汀通过抑制血管壁中发生的炎症反应来预防动脉粥样硬化的新机制。
